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Monday, March 31, 2008

Polycystic kidney disease (PKD) is a genetic disorder characterised by the growth of numerous cysts in the kidneys. The cysts are filled with fluid. PKD cysts can slowly replace much of the mass of the kidneys, reducing kidney function and leading to kidney failure.

The kidneys are two organs, each about the size of a fist, located in the upper part of a person's abdomen, toward the back. The kidneys filter wastes from the blood to form urine. They also regulate amounts of certain vital substances in the body.

When PKD causes kidneys to fail—which usually happens after many years—the patient requires dialysis or kidney transplantation. About one-half of people with the major type of PKD progress to kidney failure, also called end-stage renal disease (ESRD).

PKD can cause cysts in the liver and problems in other organs, such as the heart and blood vessels in the brain. These complications help doctors distinguish PKD from the usually harmless "simple" cysts that often form in the kidneys in later years of life.

In the United States, about 500,000 people have PKD, and it is the fourth leading cause of kidney failure. Medical professionals describe two major inherited forms of PKD and a noninherited form:

Autosomal dominant PKD is the most common inherited form. Symptoms usually develop between the ages of 30 and 40, but they can begin earlier, even in childhood. About 90 percent of all PKD cases are autosomal dominant PKD.

Autosomal recessive PKD is a rare inherited form. Symptoms of autosomal recessive PKD begin in the earliest months of life, even in the womb.

Acquired cystic kidney disease (ACKD) develops in association with long-term kidney problems, especially in patients who have kidney failure and who have been on dialysis for a long time. Therefore it tends to occur in later years of life. It is not an inherited form of PKD.

1. Autosomal Dominant Polycystic Kidney Disease

What is autosomal dominant PKD?

Autosomal dominant PKD is one of the most common inherited disorders. The phrase "autosomal dominant" means that if one parent has the disease, there is a 50-percent chance that the disease will pass to a child. At least one parent must have the disease for a child to inherit it. Either the mother or father can pass it along, but new mutations may account for one-fourth of new cases. In some rare cases, the cause of autosomal dominant PKD occurs spontaneously in the child soon after conception—in these cases the parents are not the source of this disease.

Many people with autosomal dominant PKD live for decades without developing symptoms. For this reason, autosomal dominant PKD is often called "adult polycystic kidney disease." Yet, in some cases, cysts may form earlier, even in the first years of life.

The disease is thought to occur equally in men and women and equally in people of all races. However, some studies suggest that it occurs more often in whites than in blacks and more often in females than in males.

The cysts grow out of nephrons, the tiny filtering units inside the kidneys. The cysts eventually separate from the nephrons and continue to enlarge. The kidneys enlarge along with the cysts (which can number in the thousands), while retaining roughly their kidney shape. In fully developed PKD, a cyst-filled kidney can weigh as much as 22 pounds. High blood pressure occurs early in the disease, often before cysts appear.

What are the symptoms of autosomal dominant PKD?

The most common symptoms are pain in the back and the sides (between the ribs and hips), and headaches. The dull pain can be temporary or persistent, mild or severe.

People with autosomal dominant PKD also can experience the following:

urinary tract infections

haematuria (blood in the urine)

liver and pancreatic cysts

abnormal heart valves

high blood pressure

kidney stones

aneurysms (bulges in the walls of blood vessels) in the brain

diverticulosis (small sacs on the colon)

How is autosomal dominant PKD diagnosed?

To diagnose autosomal dominant PKD, a doctor typically observes three or more kidney cysts using ultrasound imaging. The diagnosis is strengthened by a family history of autosomal dominant PKD and the presence of cysts in other organs.

In most cases of autosomal dominant PKD, the person's physical condition appears normal for many years, even decades, so the disease can go unnoticed. Physical checkups and blood and urine tests may not lead to diagnosis. The slow, undetected progression is why some people live for many years without knowing they have autosomal dominant PKD.

Once cysts have formed, however, diagnosis is possible with imaging technology. Ultrasound, which passes sound waves through the body to create a picture of the kidneys, is used most often. Ultrasound imaging employs no injected dyes or radiation and is safe for all patients, including pregnant women. It can also detect cysts in the kidneys of a foetus.

More powerful and expensive imaging procedures such as computed tomography (CT scan) and magnetic resonance imaging (MRI) also can detect cysts, but they usually are not required for diagnosis because ultrasound provides adequate information. CT scans require x rays and sometimes injected dyes.

A genetic test can detect mutations in the PKD1 and PKD2 genes. Although this test can detect the presence of the autosomal dominant PKD mutations before cysts develop, its usefulness is limited by two factors; it cannot predict the onset or ultimate severity of the disease, and no absolute cure is available to prevent the onset of the disease. On the other hand, a young person who knows of a PKD gene mutation may be able to forestall the disease through diet and blood pressure control. The test may also be used to determine whether a young member of a PKD family can safely donate a kidney to a parent. Anyone considering genetic testing should receive counselling to understand all the implications of the test.

How is autosomal dominant PKD treated?

Although a cure for autosomal dominant PKD is not available, treatment can ease the symptoms and prolong life.

Pain. A doctor will first suggest over-the-counter pain medications, such as aspirin or Tylenol. For most but not all cases of severe pain, surgery to shrink cysts can relieve pain in the back and flanks. However, surgery provides only temporary relief and usually does not slow the disease's progression toward kidney failure.

Headaches that are severe or that seem to feel different from other headaches might be caused by aneurysms, or swollen blood vessels, in the brain. Headaches also can be caused by high blood pressure. People with autosomal dominant PKD should see a doctor if they have severe or recurring headaches—even before considering over-the-counter pain medications.

Urinary tract infections. Patients with autosomal dominant PKD tend to have frequent urinary tract infections, which can be treated with antibiotics. People with the disease should seek treatment for urinary tract infections immediately, because infection can spread from the urinary tract to the cysts in the kidneys. Cyst infections are difficult to treat because many antibiotics do not penetrate into the cysts. However, some antibiotics are effective.

High blood pressure. Keeping blood pressure under control can slow the effects of autosomal dominant PKD. Lifestyle changes and various medications can lower high blood pressure. Patients should ask their doctors about such treatments. Sometimes proper diet and exercise are enough to keep blood pressure low.

End-stage renal disease. Because kidneys are essential for life, people with ESRD must seek one of two options for replacing kidney functions: dialysis or transplantation. In haemodialysis, blood is circulated into an external machine, where it is cleaned before reentering the body; in peritoneal dialysis, a fluid is introduced into the abdomen, where it absorbs wastes, and it is then removed. Transplantation of healthy kidneys into ESRD patients has become a common and successful procedure. Healthy (non-PKD) kidneys transplanted into PKD patients do not develop cysts.

2. Autosomal Recessive Polycystic Kidney Disease

What is autosomal recessive PKD?

Autosomal recessive PKD is caused by a particular genetic flaw that is different from the genetic flaw that causes autosomal dominant PKD. Parents who do not have PKD can have a child with the disease if both parents carry the abnormal gene and both pass the gene to their baby. The chance of this happening (when both parents carry the abnormal gene) is one in four. If only one parent carries the abnormal gene, the baby cannot get the disease.

The symptoms of autosomal recessive PKD can begin before birth, so it is often called "infantile PKD." Children born with autosomal recessive PKD usually develop kidney failure within a few years. Severity of the disease varies. Babies with the worst cases die hours or days after birth. Children with an infantile version may have sufficient renal function for normal activities for a few years. People with the juvenile version may live into their teens and twenties and usually will have liver problems as well.

What are the symptoms of autosomal recessive PKD?

Children with autosomal recessive PKD experience high blood pressure, urinary tract infections, and frequent urination. The disease usually affects the liver, spleen, and pancreas, resulting in low blood-cell counts, varicose veins, and haemorrhoids. Because kidney function is crucial for early physical development, children with autosomal recessive PKD are usually smaller than average size.

How is autosomal recessive PKD diagnosed?

Ultrasound imaging of the foetus or newborn baby reveals cysts in the kidneys but does not distinguish between the cysts of autosomal recessive and autosomal dominant PKD. Ultrasound examination of kidneys of relatives can be helpful; for example, a parent or grandparent with autosomal dominant PKD cysts could help confirm diagnosis of autosomal dominant PKD in a foetus or child. (It is extremely rare, although not impossible, for a person with autosomal recessive PKD to become a parent.) Because autosomal recessive PKD tends to scar the liver, ultrasound imaging of the liver also aids in diagnosis.

How is autosomal recessive PKD treated?

Medicines can control high blood pressure in autosomal recessive PKD, and antibiotics can control urinary tract infections. Eating increased amounts of nutritious food improves growth in children with autosomal recessive PKD. In some cases, growth hormones are used. In response to kidney failure, autosomal recessive PKD patients must receive dialysis or transplantation.

Genetic Diseases

Genes are segments of DNA, the long molecules that reside in the nuclei of your body's cells. The genes, through complex processes, cause chemical activities that lead to growth and maintenance of the body. At conception, DNA (and therefore genes) from both parents are passed to the child.

A genetic disease occurs when one or both parents pass abnormal genes to a child at conception. If receiving an abnormal gene from just one parent is enough to produce a disease in the child, the disease is said to have dominant inheritance. If receiving abnormal genes from both parents is needed to produce disease in the child, the disease is said to be recessive.

The chance of acquiring a dominant disease (one gene copy is enough) is higher than the chance of acquiring a recessive disease (two gene copies are needed). A child who receives only one gene copy for a recessive disease at conception will not develop the genetic disease (such as autosomal recessive PKD), but could pass the gene to the following generation.

3. Acquired Cystic Kidney Disease

What is ACKD?

ACKD develops in kidneys with long-term damage and bad scarring, so it often is associated with dialysis and end-stage renal disease. About 90 percent of people on dialysis for 5 years develop ACKD. People with ACKD can have any underlying kidney disease, such as glomerulonephritis or kidney disease of diabetes.

The cysts of ACKD may bleed. Kidney tumours, including kidney (renal) cancer, can develop in people with ACKD. Renal cancer is rare yet occurs at least twice as often in ACKD patients as in the general population.

How is ACKD diagnosed?

Patients with ACKD usually seek help because they notice blood in their urine (haematuria). The cysts bleed into the urinary system, which discolors urine. Diagnosis is confirmed using ultrasound, CT scan, or MRI of the kidneys.

How is ACKD treated?

Most ACKD patients are already receiving treatment for kidney problems. In rare cases, surgery is used to stop bleeding of cysts and to remove tumours or suspected tumours.

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